Name: tight junction proteins and cell barriers
Uploaded: 2023-04-30T11:55:38.000Z
Duration: 1 min 29 s
Channel: JoVE

In organi come i reni e l'intestino, le cellule epiteliali sono sigillate insieme con giunzioni strette per impedire il flusso di macromolecole, ioni e piccoli soluti attraverso lo spazio paracellulare.
Le giunzioni strette comprendono principalmente proteine transmembrana claudina e occludina, ciascuna con quattro alfa-eliche che attraversano la membrana.
File di claudine e occludine polimerizzano sulla membrana, formando una rete di filamenti di tenuta.
Questi filamenti si attaccano a filamenti simili di proteine sulla cellula adiacente attraverso i loro anelli extracellulari, tenendo così insieme le due membrane.
Sul lato citoplasmatico, le code C-terminali di queste proteine si associano con i domini PDZ di grandi proteine dell'impalcatura chiamate zonula occludens o ZO.
Le proteine ZO hanno più domini di legame proteico e possono quindi legare claudine, occludine, actina e altre proteine ZO, formando una rete che organizza e stabilizza questi filamenti di sigillatura.
Oltre a sigillare lo spazio paracellulare, le giunzioni strette impediscono anche il movimento laterale delle proteine, come i trasportatori del glucosio, lungo la membrana. Questo aiuta a localizzare queste proteine sulla superficie apicale dell'epitelio intestinale per l'assorbimento del glucosio.

<ol>
	<li>Sawada, Norimasa. "Malattie umane correlate alla giunzione stretta". Patologia internazionale 63.1 (2013): 1-12. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168075/">Link</a></li>
	<li>Anderson, James M. e Christina M. Van Itallie. "Fisiologia e funzione della giunzione stretta". Prospettive di Cold Spring Harbor in biologia 1.2 (2009): a002584. <a href="https://cshperspectives.cshlp.org/content/1/2/a002584.full">Link</a></li>
	<li>Mariano, Cibelle, et al. "Uno sguardo alla tricellulina e al suo ruolo nella formazione e nel mantenimento della giunzione stretta." Rivista europea di biologia cellulare 90.10 (2011): 787-796. <a href=" https://d1wqtxts1xzle7.cloudfront.net/52322075/A_look_at_tricellulin_and_its_role_in_ti20170327-17112-1qhpwe8-libre.pdf?1490608194=&response-content-disposition=inline%3B+filename%3DA_look_at_tricellulin_and_its_role_in_ti.pdf&Expires=1654205963&Signature=IelR0FUZCC6ZcqAcJvs1JTGe6liRDBX6aqaYzcw4sMZ2yqyhu5BuZ9DDbujaDRUN9SwX20yuCRLRyzxl6MWAa4QfY2cZ1wtZb4qfoi5otW~z0rhB3ba231uB1~pdP0rZpdHB4~snYhLr-~nZRsoaUqTFJmJaJXpxtHnoBGC4HFP29Q8D3q0rNHNDJGq9Qx9SfcLWmDISH7n8IfsUozT6rdpn421eOVufn5lNVunpqMX6iiRAT4D7p8bJEPpfd2~3cygJP7Ltc32RiIm2RHGvp9CRUoXs015y2aR4A7--dka7UzL97Aa~DDZ8ES90wX9D58qA~jX24DnmzNeNwlAayg__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA">Collegamento</a></li>
</ol>

giunzioni strette

Tight Junctions

Le giunzioni strette sono sigilli molecolari tra le cellule che impediscono la fuoriuscita di fluidi, ioni e altri piccoli soluti attraverso cavità e compartimenti negli organismi multicellulari. Sono composti principalmente da proteine transmembrana claudina e occludina e da altre proteine come la tricellulina e la JAM (molecola di adesione giunzionale). Tutte queste proteine sono proteine transmembrana a 4 passaggi, tranne JAM, che è una proteina transmembrana a passaggio singolo appartenente alla superfamiglia delle immunoglobuline. I domini extracellulari di queste proteine a giunzione stretta interagiscono con quelli della membrana cellulare adiacente, riunendo e sigillando così le due cellule adiacenti.

Permeabilità selettiva delle giunzioni strette

Esistono molteplici isoforme della claudina transmembrana, con un massimo di 24 tipi diversi espressi negli esseri umani. La diversità della proteina claudina conferisce permeabilità selettiva a diverse giunzioni strette. Ad esempio, la claudina-16, espressa nell'epitelio renale, aumenta la permeabilità agli ioni magnesio, consentendone così la ricaptazione dal sangue durante la filtrazione. Al contrario, la claudina-5 espressa nelle cellule endoteliali dei capillari cerebrali diminuisce selettivamente la permeabilità ionica attraverso la barriera ematoencefalica.

Giunzioni tricellulari

Oltre a sigillare gli spazi tra due cellule, le giunzioni strette sigillano anche gli spazi formati alla giunzione di tre cellule: una giunzione tricellulare. La struttura delle giunzioni tricellulari è stata osservata per la prima volta negli anni '70 utilizzando la microscopia elettronica a frattura congelata. In queste giunzioni, i trefoli sigillanti sono orientati perpendicolarmente ai trefoli delle giunzioni strette bicellulari. Il punto di contatto tricellulare forma così uno stretto tubo verticale di circa 10 nm di diametro, che controlla il movimento paracellulare delle molecole.

La tricellulina è stata la prima proteina identificata a concentrarsi in queste giunzioni tricellulari. Condivide l'omologia di sequenza con le proteine occludina e presenta quattro isoforme nell'uomo. È interessante notare che le mutazioni nel gene della tricellulina, TRIC, hanno dimostrato di causare danni all'udito, dimostrando la sua importanza nel mantenere una tenuta stagna come quella richiesta nell'organo del Corti, una struttura nell'orecchio interno.

Giunzioni strette

Le giunzioni strette sono sigilli molecolari tra le cellule che impediscono la fuoriuscita di fluidi, ioni e altri piccoli soluti attraverso cavità e compartimenti ...

Education

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Cell Biology

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Cell-Cell Interactions

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KEY TERMS AND CONCEPTS

TERMINI E CONCETTI CHIAVE

tight junction proteins and cell barriers

Tight junction proteins form seals between neighboring cells. These molecular barriers help stop fluids, ions, and other small solutes from leaking across body cavities and tissue compartments in multicellular organisms. They are an important part of cell barriers in places where controlled movement matters.

The main tight junction proteins are claudin and occludin. Other proteins include tricellulin and JAM, which stands for junctional adhesion molecule. Most of these proteins are 4-pass transmembrane proteins, meaning they cross the cell membrane four times. JAM is different because it is a single-pass transmembrane protein in the immunoglobulin superfamily. The extracellular parts of these proteins interact with matching parts on the nearby cell membrane. This brings two adjacent cells together and helps seal them.

Claudin proteins are especially important because there are many isoforms, or forms, of claudin. Humans express up to 24 different types. This diversity gives tight junctions selective permeability, which means some substances pass more easily than others. For example, claudin-16 in kidney epithelium increases permeability to magnesium ions. This helps magnesium move back into the body during filtration. In contrast, claudin-5 in endothelial cells of brain capillaries lowers ion permeability across the blood-brain barrier.

Tight junctions also seal tricellular junctions, which are the gaps where three cells meet. These junctions were first seen in the 1970s with freeze-fracture electron microscopy. At these contact points, the sealing strands run perpendicular to the strands in bicellular tight junctions. The center of the tricellular contact forms a narrow vertical tube about 10 nm wide. This structure helps control paracellular movement, which is movement between cells.

Tricellulin is the first protein known to concentrate at tricellular junctions. It is related in sequence to occludin and has four isoforms in humans. Mutations in the tricellulin gene, TRIC, can cause hearing impairment. This shows how important tight seals are in the organ of Corti, a structure in the inner ear.

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tight junctions

Tight junction proteins form seals between neighboring cells. These molecular barriers help stop fluids, ions, and other small solutes from leaking across body cavities and tissue compartments in multicellular organisms. They are an important part of cell barriers in places where controlled movement matters. The main tight junction proteins are claudin and occludin. Other proteins include tricellulin and JAM, which stands for junctional adhesion molecule. Most of these proteins are 4-pass...

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key terms and concepts

Learn how claudin, occludin, tricellulin, and JAM seal cells, control selective permeability, and support barriers like the blood-brain barrier.

Tight Junction Proteins and Cell Barriers | JoVE K12

cell biology

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Tight Junction Proteins and Cell Barriers

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